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中文摘要
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我们已经成功地创建和表征了一组单克隆抗体和IG 相关融合蛋白各种不同的技术,包括cDNA免疫,已经成功地 用于Kuchroo博士实验室制造可溶性和细胞表面蛋白的单克隆抗体。我们 已经制造出了针对小鼠、人类、大鼠和仓鼠蛋白质的抗体。此外,郑博士还成功地 产生了几十种Ig融合蛋白。了解一种新发现的蛋白质IG的生物学功能 融合蛋白已被用于鉴定分子的体外和体内功能。在这一努力中 细胞因子或细胞表面蛋白已经与IgG的重链融合,并且我们最近 在辛晓铮、Vijay Kuchroo和Terry B之间建立了一个合作核心。努力建立一个 Beth Israel Deaconess Medical移植研究中心的抗体和融合蛋白Core 布里格姆妇女医院神经疾病中心。两个中心均位于 哈佛医学院。调查人员定期开会,进行计划会议, 协商研究人员在合作生产单克隆抗体方面有着悠久的历史, 抗体和融合蛋白的许多细胞表面的目标。最近的合作导致了 TIM家族分子的单克隆抗体和IG融合蛋白的产生, 发现了在T细胞表面表达的免疫调节分子。抗体针对 可产生可作为激动剂并激活受体或拮抗剂的特异性蛋白质 并阻断分子的功能。另一方面,IG融合蛋白具有以下优点: 与天然配体结合,并可用作鉴定和分子克隆配体的工具。 此外,IG融合蛋白可作为阻断剂并干扰受体:配体的结合 因此有助于理解分子的体内功能。IG蛋白还 具有长的半衰期和最小的免疫原性,因此可以成功地在体内用于 了解新发现的分子的功能。所述抗体和IG融合蛋白是 独特的试剂,并已被证明是一个强大的工具,以促进创新的研究,在许多 领域和一些已被证明是有效的免疫调节剂,以治疗人类自身免疫性 疾病、癌症和诱导移植耐受。 抗体和融合蛋白Core的目标是为开发单克隆抗体和融合蛋白提供平台。 用于新发现的分子或基因的多克隆抗体和新型治疗性IG融合蛋白 PPG。我们的作用将是为新鉴定的蛋白质提供抗体和融合蛋白。而 由核心产生的蛋白质将不在GMP设施中生产,用于生产的细胞系 符合FDA标准。因此,将来可以很容易地进行临床试验。
英文摘要
We have been successful in our effort to create and characterize a panel of monoclonal antibodies and Ig related fusion proteins. Various different techniques, including cDNA immunization have been successfully used in Dr. Kuchroo' laboratory to make monoclonal antibodies to soluble and cell surface proteins. We have made antibodies to mouse, human, rat and hamster proteins. In addition, Dr. Zheng has successfully generated dozens of Ig-fusion proteins. To understand biological functions of a newly identified protein, Ig fusion proteins have been utilized for identifying in vitro and in vivo function of the molecules. In this effort cytokines or cell surface proteins have been fused with the heavy chain of IgG, and we have recently established a collaborative core between Xin Xiao Zheng, Vijay Kuchroo and Terry B. Strom to build a antibody and fusion protein Core within the Transplant Research Center at Beth Israel Deaconess Medical Center and Center for Neurologic Diseases, Brigham and Women's Hospital. Both Centers are located in the Harvard Institutes of Medicine. The investigators meet regularly for planned meeting for impromptu consultation. The investigators have a long history of working together and producing monoclonal antibodies and fusion proteins to a number of cell surface targets. The recent collaboration has led to the generation of monoclonal antibodies and Ig fusion proteins to TIM family of molecules, a family of newly discovered immunoregulatory molecules expressed on the surface of T cells. The antibodies against specific proteins can be generated that can act as an agonist and activate the receptor or an antagonist and block the function of the molecule. Ig fusion proteins, on the other hand, have an advantage of binding to the natural ligand and can be utilized as tools to identify and molecularly clone the ligand. Furthermore, Ig fusion proteins can act as blocking agents and interfere with the binding of receptor:ligand interaction and therefore help in the understanding the in vivo function of the molecule. Ig proteins also have long half-lives and minimal immunogenicity, therefore can be used successfully in vivo for understanding the function of the newly identified molecule. The antibodies and Ig fusion proteins are unique reagents and have been proven to be a powerful tools to facilitate innovative research in many fields and some have proven to be potent immunomodulatory reagents to treat human autoimmune diseases, cancer and induce transplantation tolerance. The goals of antibody and fusion protein Core will be to provide a platform for developing monoclonal and polyclonal antibodies and novel therapeutic Ig.fusion proteins for newly discovered molecules or genes for PPG. Our role will be to provide antibodies and fusion proteins for newly identified proteins. While the proteins produced by the core will not be manufactured in a GMP facility, the cell lines used for production will meet FDA standards. Thus it will be possible to easily progress to a clinical trial in the future.
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Effector Function of Regulatory T Cells in EAE
  • 批准号:
    9470744
  • 项目类别:
  • 资助金额:
    $28.25万
  • 财政年份:
    2018
  • 负责人:
    Mohamed Oukka
  • 依托单位:
Role of Dock8 in EAE
  • 批准号:
    9125526
  • 项目类别:
  • 资助金额:
    $28.94万
  • 财政年份:
    2016
  • 负责人:
    Mohamed Oukka
  • 依托单位:
Role of Dock8 in EAE
  • 批准号:
    9324123
  • 项目类别:
  • 资助金额:
    $24.11万
  • 财政年份:
    2016
  • 负责人:
    Mohamed Oukka
  • 依托单位:
Role of S1P1 in the function of Regulatory T cells in Autoimmune Encephalomyeliti
  • 批准号:
    8889765
  • 项目类别:
  • 资助金额:
    $48.5万
  • 财政年份:
    2014
  • 负责人:
    Mohamed Oukka
  • 依托单位:
国内基金
海外基金
Agonist-GPR119-Gs复合物的结构生物学研究
  • 批准号:
    32000851
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    24.0万元
  • 批准年份:
    2020
  • 负责人:
    乔安娜
  • 依托单位: